1. Technical Field
The present invention relates to a monoclonal antibody having an activity of neutralizing human immunodeficiency virus (HIV).
2. Background Art
Acquired Immunodeficiency Syndrome (AIDS) is a pathologic condition caused by chronic infection with Lentivirus called Human Immunodeficiency virus (HIV). In recent years, an antiviral agent for inhibiting the growth of HIV has been developed, and thus it has become possible to inhibit the onset of AIDS. However, even using a strong antiviral agent, it is still difficult to completely cure HIV, and the antiviral treatment needs to be continued on a lifetime basis. On the other hand, it has become clear that such antiviral agents are problematic in terms of the emergence of drug-resistant virus and chronic toxicity caused by the long-term use thereof. Accordingly, the current antiviral treatment has been still insufficient. Moreover, such antiviral agents are expensive, and thus the long-term use thereof is substantially impossible in developing countries. Under such circumstances, the development of a vaccine for prevention of HIV infection has been a worldwide issue, and also, it has been desired to develop a new therapeutic agent having no side effects.
There have been reported various monoclonal antibodies that neutralize HIV infection (Burton, D R. et al., Nat. Immunol. 5, pp. 233-236, 2004; Zolla-Pazner, S. et al., Nat. Rev. Immunol. 4, pp. 199-210, 2004; Eda, Y. et al., J. Virol. 80: 5552-5562, 2006).
Depending on their target molecules, such monoclonal antibodies are broadly classified into: antibodies against the variable region such as V1/V2 or V3 of an HIV envelope protein gp120; antibodies against the CD4-binding site (CD4bs) thereof; and antibodies against CD4i (epitope appearing after the binding of CD4-gp120). On the other hand, the neutralizing activity of an antibody against the MPR (membrane proximal region) of a transmembrane protein gp41 has also been published. Among these antibodies, antibodies that have seemed to show a cross-reaction include: 447-52D and KD-247 in the case of V3 antibodies; b12 in the case of CD4bs antibodies; 2F5 and 4E10 in the case of gp41-MPR antibodies; and 2G12 in the case of anti-gylcan antibodies. The V3 antibodies have cross-reactivity, but these antibodies have been problematic in that viral strains with which they can react are limited. On the other hand, since the gp41-MPR antibodies have had a cross-reaction with many clinically isolated strains, they have become a focus of attention over recent years. However, it has been currently reported that such antibodies cross-react with the membranelipids of host cells, and that, as a matter of fact, an autoantibody cross-reacts with the gp41 of HIV. Furthermore, b12 has a long CD3 portion consisting of 18 amino acids, and thus, its cross-reactivity with an autoantigen has been suggested (Haynes, B F et al., Science 308, pp. 1906-1908, 2005).    Non-Patent Document 1: Burton, D R. et al., Nat. Immunol. 5, pp. 233-236, 2004    Non-Patent Document 2: Zolla-Pazner, S. et al., Nat. Rev. Immunol. 4, pp. 199-210, 2004    Non-Patent Document 3: Eda, Y. et al., J. Virol. 80: 5552-5562, 2006    Non-Patent Document 4: Haynes, B F et al., Science 308, pp. 1906-1908, 2005